Christopher Hill also said North Korea - one of the world's most isolated countries - appeared to be opening up, and said efforts had begun towards removing the communist regime from Washington's list of countries sponsoring terrorism.
"By Monday morning, they will begin their work," Hill said, referring to the U.S. team that arrived in Pyongyang on Thursday. "It's a very big day because it's the first time it's actually going to start disabling its nuclear program," he said.
The North shut down the reactor in July, and promised to disable it by year's end in exchange for energy aid and political concessions from other members of talks on its nuclear program: the U.S., China, Japan, South Korea and Russia.
Disabling the reactor would mark a further breakthrough in efforts to convince the North to scale back its nuclear program. The country conducted its first-ever nuclear test in October of last year.
Hill said the U.S. hoped to disable North's uranium enrichment program by the end of the year, not just its plutonium-production facilities at Yongbyon.
"By the end of the year, on the road to denuclearization, we hope to have arrived at an important milestone, where there is a complete disablement of the Yongbyon facilities, a full list of additional facilities for disablement, and that uranium enrichment is also resolved to mutual satisfaction," Hill said.
Hill said he hoped to start talks with North Korea in the next weeks over the list of facilities - another promise made by the regime under a Feb. 13 agreement - and that it should include programs other than the ones at Yongbyon, as well as nuclear materials.
"Yongbyon is not the only nuclear facility that needs to be put out of commission," Hill said.
Hill also said the U.S. remained worried over the alleged transfer of nuclear technology and materials from North Korea to countries like Syria. Last month, a news report said Israeli strikes in Syria had targeted a partially built nuclear reactor, made with North Korean help, citing U.S. and foreign officials.
Still, North Korea appeared to be opening up through the regional engagement over its nuclear program, Hill said, pointing to a flurry of diplomatic activity by Pyongyang in recent months.
The North has opened or restored relations with five countries since July, and senior officials have visited Russia, Southeast Asia, Africa and the Middle East - a rare burst of international activity by one of the world's most isolated nations.
"As they participate in the six-party process, I think there is a desire to overcome their isolation," Hill said. He warned, however, the process would be slow.
The envoy said U.S. lawyers were working with the North to prepare to remove it from a U.S. list of states sponsoring terrorism, but that Pyongyang ultimately needed to meet requirements stipulated under U.S. law.
Taking Pyongyang off the terror list, long a key demand of the North, was one of a series of economic and political concessions offered for the country to disable its nuclear reactor that produces plutonium for bombs.
He said the U.S. would not strike North Korea from the list - or form diplomatic ties - without the regime's full denuclearization.
Meanwhile, Hill stressed that disarmament - which he said would take two months - was just the first step, and he expected further progress toward the complete denuclearization of the Korean peninsula to begin immediately after the Dec. 31 deadline.
"I need to make sure that dismantlement and abandonment phase starts on January 1, or maybe January 2," Hill said. "From disabling we will go on a seamless continuum toward dismantlement, that is taking these facilities apart and making sure they are never again used for the purpose they were used for before," he said.
Under a February agreement, North Korea pledged to abandon its nuclear ambitions in exchange for the equivalent of 1 million tons of oil and political concessions. But at the talks in the Korean border village of Panmunjom, it agreed to accept half of the aid in energy-related equipment and other items.
The communist government has already shut down its sole operating reactor in Yongbyon under an initial phase of the Feb. 13 deal in return for a shipment of 50,000 tons of oil aid from South Korea.
The Yongbyon complex is believed to have produced enough plutonium for more than a dozen bombs - including the device North Korea detonated a year ago to prove its long-suspected nuclear capability.